PURPOSE: Abiraterone is the active metabolite of the pro-drug abiraterone acetate (AA) and a selective inhibitor of CYP17, a key enzyme in testosterone synthesis, and improves overall survival in postdocetaxel metastatic castration-resistant prostate cancer (mCRPC).
This open-label, single-arm phase 1b study was conducted to assess the effect of AA and abiraterone on the QT interval.
METHODS: The study was conducted in 33 patients with mCRPC. Patients received AA 1,000 mg orally once daily + prednisone 5 mg orally twice daily. Electrocardiograms (ECGs) were collected in triplicate using 12-lead Holter monitoring. Baseline ECGs were obtained on Cycle 1 Day-1. Serial ECG recordings and time-matched pharmacokinetic (PK) blood samples were collected over 24 h on Cycle 1 Day 1 and Cycle 2 Day 1. Serial PK blood samples were also collected over 24 h on Cycle 1 Day 8.
RESULTS: After AA administration, the upper bound of the 2-sided 90 % confidence interval (CI) for the mean baseline-adjusted QTcF change was < 10 ms; no patients discontinued due to QTc prolongation or adverse events. No apparent relationship between change in QTcF and abiraterone plasma concentrations was observed [estimated slope (90 % CI): 0.0031 (-0.0040, 0.0102)].
CONCLUSIONS: There is no significant effect of AA plus prednisone on the QT/QTc interval in patients with mCRPC.
Written by:
Tolcher AW, Chi KN, Shore ND, Pili R, Molina A, Acharya M, Kheoh T, Jiao JJ, Gonzalez M, Trinh A, Pankras C, Tran N. Are you the author?
South Texas Accelerated Research Therapeutics (START), Center for Cancer Care, 4383 Medical Drive, San Antonio, TX, 78229, USA.
Reference: Cancer Chemother Pharmacol. 2012 Aug;70(2):305-13.
doi: 10.1007/s00280-012-1916-9
PubMed Abstract
PMID: 22752297
UroToday.com Prostate Cancer Section